The Wilms tumor-suppressor gene WT1, a key player in renal development, also has a crucial role in maintenance of the glomerulus in the mature kidney. However, molecular pathways orchestrated by WT1 in podocytes, where it is highly expressed, remain unknown. Their defects are thought to modify the cross-talk between podocytes and other glomerular cells and ultimately lead to glomerular sclerosis, as observed in diffuse mesangial sclerosis (DMS) a nephropathy associated with WT1 mutations.
A murine model of Denys-Drash syndrome reveals novel transcriptional targets of WT1 in podocytes.
Sex, Specimen part
View SamplesCancer cells have abnormal gene expression profiles, however, the transcription factors and the architecture of the regulatory network that drive cancer specific gene expression is often not known. Here we studied a model of Ras-driven invasive tumorigenesis in Drosophila epithelial tissues and combined in vivo genetics with high-throughput sequencing and computational modeling to decipher the regulatory logic of tumor cells. Surprisingly, we discovered that the bulk of the tumor specific gene expression is driven by an ectopic network of a few transcription factors that are overexpressed and/or hyperactivated in tumor cells. These factors are Stat, AP-1, the bHLH proteins Myc and AP-4, the nuclear hormone receptor Ftz-f1, the nuclear receptor coactivator Taiman/AIB1, and Mef2. Notably, many of these transcription factors are also hyperactivated in human tumors. Bioinformatics analysis predicted that these factors directly regulate the majority of the tumor specific gene expression, that they are interconnected by extensive cross-regulation, and that they show a high degree of co-regulation of target genes. Indeed, the factors of this network were required in multiple epithelia for tumor growth and invasiveness and knock-down of individual factors caused a reversion of the tumor specific expression profile, but had no observable effect on normal tissues. We further found that the Hippo pathway effector Yki/Sd was strongly activated in tumor cells and initiated cellular reprogramming by activating several transcription factors of this network. Thus, modeling regulatory networks identified an ectopic yet highly ordered network of master regulators that control tumor cell specific gene expression. Overall design: RNA-seq gene expression profiling across Drosophila 3rd instar larval wild type wing discs and genetic perturbations of wts.
An Ectopic Network of Transcription Factors Regulated by Hippo Signaling Drives Growth and Invasion of a Malignant Tumor Model.
Subject, Time
View SamplesGene expression study of human and Chimpanzee iPS cell.
New type of Sendai virus vector provides transgene-free iPS cells derived from chimpanzee blood.
Specimen part
View SamplesTo evaluate gene expression changes in mixed tissue samples used as process controls in male Sprague Dawley rats over time.
Assessment of repeated microarray experiments using mixed tissue RNA reference samples.
No sample metadata fields
View SamplesThe female germline undergoes a unique line of differentiation processes that endows totipotency to the egg. During these processes, biologically significant events such as meiosis and oocyte growth are controlled in an orderly manner, with any disorder causing infertility and developmental arrest of the next generation. Reconstitution in vitro of the entire process of oogenesis from pluripotent stem cells is a key achievement in stem cell biology and regenerative medicine, but a robust and reproducible culture system has not been established. Here, we report successful reconstitution in vitro throughout the entire process of oogenesis from pluripotent stem cells, yielding in vitro-produced eggs that gave rise to healthy pups. Moreover, the pluripotent stem lines were re-derived from the in vitro-generated eggs, thereby reconstituting one generation on a dish. This culture system will provide a unique platform for elucidating the molecular mechanisms underlying totipotency and could open an avenue to producing vast numbers of eggs in vitro. Overall design: The transcriptomes of ES cells (ESCs), primordial germ cell-like cells at day 6 of differentiation (PGCLCs_d6), PGCLCs aggregated with gonadal somatic cells (PGCLCs_agg3), in vitro-produced primary oocytes in secondary follicles (vitro_2nd_fol_oocyte) and MII oocytes (vitro MII oocytes) are determined by RNA-seq analysis. For comparison, the transcriptomes of E12.5 PGCs (vivo_E12.5_PGCs), P8 primary oocytes (vivo_2nd_fol._oocyte) and MII oocytes (vivo_MII_oocyte) in vivo are also determined. Biologically triplicated (rep1-3) or duplicated (rep1-2) samples are sequnced simultaneously.
Mechanical stress accompanied with nuclear rotation is involved in the dormant state of mouse oocytes.
Specimen part, Cell line, Subject
View SamplesAnalysis of umbilical vein endothelial cells (HUVEC) treated with Egr-3 siRNA under the VEGF treatment for 0,1, and 4 h. Egr-3, a member of early growth response family, is immediately and dramatically induced by VEGF in HUVEC, which regulates expression of many genes related to endothelial activation.
Vascular endothelial growth factor activation of endothelial cells is mediated by early growth response-3.
No sample metadata fields
View SamplesRhizoctonia solani is an economically important soil-borne necrotrophic fungal pathogen, with a broad host range and for which little effective resistance exists in crop plants. Arabidopsis is resistant to the R. solani AG8 isolate but susceptible to R. solani AG2-1. Affymetrix microarray analysis was performed to determine genes that are affected in common and specifically by AG8 and AG2-1.
Genetic and genomic analysis of Rhizoctonia solani interactions with Arabidopsis; evidence of resistance mediated through NADPH oxidases.
Age, Specimen part, Treatment
View SamplesL-Ser deficiency leads to growth arrest, tissue malformation and embryonic lethality in mice. However, the molecular mechanism by which L-Ser deficiency impairs basic cellular function remains largely unexplored.
Microarray data on altered transcriptional program of Phgdh-deficient mouse embryonic fibroblasts caused by ʟ-serine depletion.
Specimen part
View SamplesAn branched-chain amino acids auxotroph eca39 mutant fission yeast exhibits an unusual adaptive growth phenotype on solid minimal media containing Ile, Leu and Val when other strains are growing nearby.
The SAGA histone acetyltransferase complex regulates leucine uptake through the Agp3 permease in fission yeast.
No sample metadata fields
View SamplesSASL1 is highly metastatic to lymph nodes. ACC2 is not metastatic. We compared gene expression on cultured cells to identify genes associated to metastatic spread patterns.
Premetastatic vasculogenesis in oral squamous cell carcinoma xenograft-draining lymph nodes.
Specimen part, Cell line
View Samples